Cancer is characterized by rapidly-proliferating cell growth in the body. Cancer is often able to invade other tissues from its original location and, in a process called metastasis, spread to other parts of the body through blood and lymphatics. Despite decades of intensive scientific and clinical research, cancer remains a major health threat to the public. There are many types of cancer, which may be classified in pathology and clinical diagnosis into carcinoma, sarcoma, leukemia, lymphoma and myeloma, and malignant tumors of the central nervous system. While significant advancements have been made in cancer prevention and treatment, cancer remains a challenging disease to both the patient and the healthcare provider. Cancer is the leading disease of mortality in all countries of the world. (Ferlay, et al. 2010 Int. J. Cancer 127, 2893-2917.)
Currently, four standard approaches have been proposed for cancer treatment: surgery, chemotherapy, radiation therapy, immunotherapy and biologic therapy. Among various cancer treatments, chemotherapy is an indispensable choice for most cancer cases because of its high efficiency. Unfortunately, due to the small molecular size of free anticancer drugs, conventional chemotherapy suffers from several limitations including poor bioavailability, rapid blood/renal clearance, non-specific selectivity, low accumulation in tumors, severe MDR, and adverse side effects for healthy tissues. To address these limitations, some nano-vehicles including water-soluble polymers, liposomes, vesicles, polymeric nanoparticles and inorganic materials have been used as drug carriers. (Park, et al. 2008 Prog. Polym. Sci. 33, 113-137; Hubbell, et al. 2012 Science 337, 303-305; Tong, et al. 2007 Polym. Rev. 47, 345-381; Riehemann, et al. 2009 Angew. Chem., Int. Ed. 48, 872-897; Fox, et al. 2009 Acc. Chem. Res. 42, 1141-1151; Lutz, et al. 2008 Prog. Polym. Sci. 33, 1-39; Kiick, et al. 2007 Science 317, 1182-1183; Lee, et al. 2005 Nat. Biotechnol. 23, 1517-1526; Zhou, et al. 2010 Adv. Mater. 22, 4567-4590; Liu, et al. 2010 Biomaterials 31, 5643-5651; Lee, et al. 2007 J. Am. Chem. Soc. 129, 15096-15097; Volodkin, et al. 2009 Angew. Chem., Int. Ed. 48, 1807-1809; Linderoth, et al. 2009 J. Am. Chem. Soc. 131, 12193-12200; Holme, et al. 2012 Nat. Nanotech. 7, 536-543; Song, et al. 2012 J. Am. Chem. Soc. 134, 13458-13469; Kataoka, et al. 2001 Adv. Drug Deliv. Rev. 47, 113-131; Griset, et al. 2009 J. Am. Chem. Soc. 131, 2469-2471; Tong, et al. 2008 Angew. Chem., Int. Ed. 47, 4830-4834; Chen, et al. 2008 J. Am. Chem. Soc. 130, 16778-16785; Kim, et al. 2010 Nat. Nanotech. 5, 465-472.)
With the help of these nano-vehicles, drugs can be delivered to the action sites of body via physical entrapment or chemical conjugation, demonstrating better therapeutic efficacy against tumors and fewer side effects over free drugs. (Wang, et al. 2011 Biomacromolecules 12, 1370-1379; Shen, et al. 2010 J. Am. Chem. Soc. 132, 4259-4265; Li, et al. 2011 Biomacromolecules 12, 2016-2026; Du, et al. 2011 J. Am. Chem. Soc. 133, 17560-17563; Singer, et al. 2001 J. Control. Release 74, 243-247; Paranjpe, et al. 2005 Anticancer Drugs 16, 763-775; Khandare, et al. 2006 J. Pharmacol. Exp. Ther. 317, 929-937.) However, almost all carriers have no therapeutic efficacy by themselves. Even worse, a lot of carriers with low drug loading capacity may arouse side-effects to kidneys and other organs in the course of degradation, metabolism and excretion, such as high toxicity and serious inflammation. (Greenwald, et al. 2003 Adv. Drug Deliv. Rev. 55, 217-250; Yu, et al. 2005 J. Control. Release 110, 90-102.)
There remains an ongoing unmet need for novel and effective antitumor therapeutics.